Metagenomic analysis reveals presence of different animal viruses in commercial fetal bovine serum and trypsin

Abstract

Animal-derived biological products, such as fetal bovine serum (FBS) and trypsin, are important supplements for scientific, pharmaceutical, and medical use. Although preventive guidelines and tests are implemented to reduce potential viral contamination in these biologicals, they do not target unusual or emerging viruses, leading to safety concerns. Using unbiased metagenomics, we investigated the presence of viruses in recently collected commercial FBS and trypsin samples from different geographic regions. In total, we detected viral sequences belonging to Parvoviridae, Anelloviridae, Flaviviridae, Herpesviridae, Caliciviridae, Nodaviridae, Rhabdoviridae, and Paramyxoviridae, including several viruses related to bovine diseases, viruses of potential human and insect origin, and viruses of unknown origin. Bovine parvovirus 3 and bosavirus were detected with high frequency and abundance in FBS, necessitating more stringent testing for these parvoviruses during production. Both bovine norovirus and bovine viral diarrhea virus 1 displayed relatively high genetic distance to closest hits, indicating the presence of new genotypes in farm animals. While the origin of novel lyssavirus and Nipah virus is unclear, their presence raises the possibility of the introduction of pathogenic animal-derived viruses into biologicals. Our results showed relatively widespread contamination of different viruses in biologicals, underscoring the need for robust safety protocol alternatives, such as metagenomic sequencing, to monitor emerging viruses.

Keywords: Biosafety; FBS; Trypsin; Viral contaminations; Virome.

Figure 1

Profiles of all viruses in different sample pools and geographic regions

Figure 2

Evolutionary relationships of all parvoviruses found in this study with representative viruses from Parvoviridae

Figure 3

Evolutionary relationship of newly described BVDV, bovine norovirus, and lyssavirus